Regulation of Prion Protein Expression in CNS due to Mouse Hepatitis Virus infection

Jana, Soumen (2015) Regulation of Prion Protein Expression in CNS due to Mouse Hepatitis Virus infection. Masters thesis, Indian Institute of Science Education and Research Kolkata.

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Abstract

Prion protein (PrP), a glycosylphosphatidyl inositol (GPI) anchored cell membrane protein is encoded by PRNP gene and constitutively expressed in central nervous system (CNS). PrP is known to be important for astrocyte development, synapse formation, myelin sheath maintenance and iron homeostasis in the CNS. It is also known to be overexpressed in some neurodegenerative/ neuroinflammatory diseases. But the underlying mechanism is not very clearly known. Mouse hepatitis virus (MHV) infection in the mouse is one of the best studied experimental animal models to understand the mechanism of neuroinflammation and chronic demyelination. One of our current studies on Affymetrix microarray analysis of acute (day 6 post infection) MHV induced inflamed spinal cord tissue revealed that there is a significant upregulation of PRNP gene compare to mock infected control. In contrast, at day 30 post infection there is no significant differences in the expression of PRNP gene between the infected and mock infected mice which signifies that PRNP gene/ PrP may play a significant role in MHV induced acute neuroinflammation. To determine the role of PRNP gene /PrP in individual neural cell types Neuro2A (N2A; Neuronal) C8D1A (astrocytic), and N9 (microglial) cell lines were chosen as cell culture model. Real time PCR, immunohistochemistry and immunoblotting data revealed that all three cell lines express PRNP gene /PrP. Upon infection with MHV, PrP expression was significantly upregulated only in N9 cells. These data imply that the upregulation what was observed in vivo spinal cord tissue could be due to the effect of PrP upregulation in Microglia/macrophage. Real time PCR data of PRNP gene in N2A, and C8D1A also corroborate these findings. Further studies are going on to study the differential effect of upregulation and down regulation of PrP in different neural cells and its role in neuroinflammation.

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